| Background:Autoimmune pancreatitis(AIP)is a type of pancreatitis involving autoimmune mechanisms,accounting for 5%to 6%of chronic pancreatitis.Type 1 AIP is a pancreatic manifestation of immunoglobulin G4-related disease(IgG4-RD).Peripancreatic vascular involvement(PVI)is a highly characteristic clinical feature of type 1 AIP.However,the presence of PVI can make it difficult to distinguish AIP from pancreatic malignancy,as malignant tumors also have biological behaviors that can invade vessels.Despite this,there have been few reports focusing on PVI.This study aimed to retrospectively review and analyze the clinical characteristics of type 1 AIP patients and identify important factors associated with PVI.Additionally,as the pancreas is affected in this disease,impaired glucose tolerance or diabetes mellitus(DM)is frequently observed in type 1 AIP patients.DM can be the first even the only clinical manifestation of AIP at diagnosis,and the response to corticosteroid treatment(CST)for AIP varies,with differences in prognosis.However,evidence regarding whether CST for AIP can improve or worsen DM is still insufficient.In this context,this study aims to explore the characteristic differences between newly developed DM and pre-existing DM in AIP patients,and to preliminarily evaluate the effect of CST on the prognosis of DM through the demonstration and analysis of clinical features.Methods:This retrospective study included 101 cases of type 1 AIP patients who were hospitalized in the Department of Gastroenterology,Peking Union Medical College Hospital between January 2013 and December 2018.Detailed information was extracted from the medical record system,including demographic,clinical,laboratory,and imaging data.All patients were divided into non-PVI and PVI groups,and potential risk factors for PVI in AIP patients were analyzed through clinical data.Patients were also divided into three groups based on the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The factors associated with cDM in AIP patients were analyzed through the analysis of clinical data among the three groups.In addition,the predictive factors for the improvement or worsening of DM after steroid therapy for AIP were explored.Results:Among 101 cases of type 1 AIP patients,52(51.5%)had PVI,with a male-female ratio of 5.5:1 and a mean age of 58.37±8.68 years.Compared with the non-PVI group,the PVI group had a higher proportion of pancreatic tail involvement(80.8%vs.57.1%,P=0.010),a higher incidence of splenomegaly(28.8%vs.4.1%,P=0.001),and lower levels of peripheral blood white blood cell(WBC)count(5.96±1.54×109 vs.6.80±2.01×109,P=0.020).Multivariate logistic analysis revealed that pancreatic tail involvement(OR,3.06;95%CI,1.17-8.02;P=0.023)and splenomegaly(OR,8.23;95%CI,1.67-40.51;P=0.010)were both risk factors for PVI in type 1 AIP patients.A total of 18 out of 25 patients in PVI group who underwent corticosteroid treatment and no less than 6 months radiological follow-up showed improvement in vascular lesions,and no case exhibited exacerbation of PVI lesions during follow-up.Among 101 patients with type 1 AIP,a total of 52 patients(51.5%)were diagnosed with DM at the time of AIP diagnosis,among which the cDM group had 36 patients,accounting for the majority of the DM group(69.2%).The incidence of diffuse pancreatic swelling(diffuse type)in the cDM group was significantly higher than that in the pDM group(72.2%vs.37.5%,P=0.018)and the nDM group(72.2%vs.51.0%,P=0.049).At the same time,the proportion of pancreatic body/tail involvement in the cDM group was also significantly higher than that in the pDM group(91.7%vs.56.3%,P=0.009)and the nDM group(91.7%vs.69.4%,P=0.013).Of the 48/52 AIP patients with DM,CST was administered.By comparing the clinical characteristics of the DM improvement group with those of the non-improvement group and conducting univariate and multivariate analysis,it was found that elevated serum GGT levels at diagnosis(OR,0.032;95%CI,0.003-0.412;P=0.008)and pancreatic atrophy after steroid treatment(OR,0.027;95%CI,0.003-0.295;P=0.003)were both independent predictors of lower likelihood of DM improvement after steroid treatment.Conclusion:The incidences of PVI and DM in type 1 AIP patients are relatively high,and their occurrence is correlated with some clinical characteristics.Clinicians should pay attention to the occurrence of complications and their prognosis in type 1 AIP patients.PVI in some patients can improve after steroid treatment.CST has a beneficial effect on DM control in some type 1 AIP patients with cDM at the time of diagnosis,but they can also cause steroid-related DM in some patients.Therefore,when treating type 1 AIP patients,it is necessary to evaluate the pros and cons of CST and individualize the treatment accordingly.Background:IgG4-RD is an immune-mediated disease characterized by fibro-inflammatory lesions that can occur in various organs,including the salivary/lacrimal glands,orbit,pancreas and biliary tract,aorta,kidneys,meninges,and thyroid.Type 1 AIP is a manifestation of IgG4-RD.Elevated serum IgG4 levels can provide important clues for diagnosing type 1 AIP and IgG4-RD,but clinical diagnosis or appropriate disease classification based on a single indicator is difficult.The diagnosis of IgG4-RD still requires comprehensive examinations including histology,imaging,and serology,to complete the exclusion of potential malignancies,infections,or other immune-mediated diseases.Meanwhile,with the further understanding of disease pathophysiology and the availability of highthroughput diagnostic platforms,many new blood biomarkers have been investigated and described in IgG4-RD in recent years.Chemokines are a class of small molecule cytokines or signaling proteins,and high levels of chemotactic factor expression have been observed in many human autoimmune diseases,such as rheumatoid arthritis,systemic lupus erythematosus,and systemic sclerosis.Chemokines and their receptors are believed to induce immune cell infiltration into affected organs in these diseases.CCL17,CCL26,CXCL12,CXCL13 have been reported to be associated with IgG4-RD.However,previous studies have mostly focused on the specific expression of one or a few chemokines in IgG4-RD or AIP patients and their clinical correlations,with conflicting conclusions.Due to the complex regulatory mechanisms of adaptive immunity,the interaction and regulation between various cells and cytokines are multidimensional and multi-directional.Therefore,this study aims to use multi-factor detection as an efficient technique to preliminarily describe the chemokines profile of type 1 AIP compared to healthy controls and pancreatic cancer in a panoramic range,providing a reference and data basis for subsequent mechanistic exploration and clinical application.Methods:Thirty-six patients with type 1 AIP,18 patients with pancreatic cancer,and 18 healthy controls matched in gender and age with type 1 AIP patients were prospectively enrolled.Peripheral blood was collected before initial treatment,and the plasma expression levels of 40 kind of cytokines/chemokines were quantitatively measured using Luminex technology and multi-factor reagent kit.Statistical tests were used to compare differences between groups and screen for cytokines/chemokines with elevated expression in type 1 AIP patients and further analyze their correlation with IgG4 levels.ROC curve analysis was used to assess the diagnostic efficiency of the detected chemotactic factors as AIP diagnostic indicators and to preliminarily evaluate their potential as biomarkers.Heat maps were used to preliminarily depict the relative levels of cytokines and chemotactic factors among the type 1 AIP,pancreatic cancer,and healthy control groups.Results:When comparing the AIP group with the PC and HC groups,the levels of 15 kind of factors,including CCL1,CCL3,CCL19,CCL23,CCL26,CCL27,CXCL2,CXCL6,CXCL9,CXCL13,IL-1β,IL-4,IL-8/CXCL8,IL-10,and GM-CSF,in AIP plasma were significantly higher than those in the HC group(P<0.05).The differences in the levels of 9 kind of factors,including CCL2,CCL13,CCL15,CCL17,CCL21,CXCL1,CXCL12,CXCL2,and IL-4 in AIP plasma compared to PC plasma were significant(P<0,05).Specifically,the levels of CCL13,CCL17,IL-4,CXCL1,and CXCL2 in AIP plasma were significantly higher than those in PC plasma,whereas the levels of CCL2,CCL15,CCL21,and CXCL12 in PC plasma were significantly higher than those in AIP plasma.The levels of IgG4 in type 1 AIP patients were significantly positively correlated with the levels of CCL19(r=0.5418,P=0.0006)and CXCL13(r=0.6220,P<0.0001).The ROC curves indicated that the AUC of CXCL13,CCL3,IL-4,IL-8,and CCL19 were all more than 0.8 and statistically significant(P<0.001).Among these factors,CCL3 had the highest diagnostic sensitivity(89%)with a cut-off value of 2.64 pg/ml,while IL-4 had the highest specificity(100%)with a cut-off value of 48.67 pg/ml.Conclusion:The expression profiles of peripheral blood chemokines and cytokines in type 1 AIP patients exhibit characteristics that are distinct from those of healthy individuals and pancreatic cancer patients.Some chemokines in the peripheral blood of AIP patients are significantly correlated with serum IgG4 levels.The differentially expressed chemokines in AIP patients may serve as promising biomarkers for diagnosis and disease monitoring and provide important clues and background for the mechanistic study of the disease. |
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